lundi 26 septembre 2016

Manquements sur l'intégrité des données pour ce fabricant chinois...

Des remarques d'inspection de la US FDA mettent encore en cause les pratiques de "data and record management" pour ce fabricant chinois d'API :

1.    Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
 
Your quality control laboratory failed to record and maintain complete data from analyses of your (b)(4) ((b)(4)) API. For example:
  • Prior to conducting official analyses,your quality control laboratory performed “experimental” analyses on product batches to assess whether your API met specifications, but failed to document these “experimental” tests in official laboratory records or to justify their exclusion. Our investigator found the results of 2,404 high performance liquid chromatography (HPLC) injections in a folder titled “Experimental” on instrument SZG-002-006l. Your quality unit indicated that these “experimental” injections were being conducted in all (b)(4)chromatographic units in your quality control laboratory. Your management provided different explanations in an attempt to justify the practice, including “fear” that the sample results would not pass.
  • Our review of the audit trails of chromatographic systems SZG-002-009, -010, -011, and -012 documented that your laboratory analysts deleted raw chromatographic data on multiple occasions. Your firm indicated that analysts may have been testing the system and may have deleted associated files. You also indicated that the deleted files may represent aborted analyses. However, we documented that some audit trail entries of deleted raw data files contained batch numbers for actual batch samples being tested. There is no assurance that laboratory records and raw data are accurate and valid... 
2.    Failure to follow and document laboratory controls at the time of performance, and failure to document and explain any departures from laboratory procedures.
 
During the inspection, your firm provided our investigator a chromatogram for an assay analysis of (b)(4) batch(b)(4) dated August 30, 2014, at 9:46:39 a.m. Your firm later submitted to FDA a different chromatogram corresponding to the same analysis, instrument, date, time, and batch. The second chromatogram appears exactly the same as the one provided during the inspection, but it includes a different method file name, column type and serial number, and system temperature. Both versions of these documents cannot represent the actual assay analysis that you conducted for batch (b)(4) on August 30, 2014, at 9:46:39 a.m...

Plus d'informations ici.

lundi 12 septembre 2016

Des nouvelles injonctions sur la "data integrity"...

Pour ce laboratoire indien, dans le cas des accès à des fichiers contenant des données réglementées (APR) :

4.    Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).

For example, the computer in your quality unit area did not have controls to restrict access and prevent unauthorized changes to data files and folders. All employees had access to your Annual Product Review (APR) spreadsheet. The desktop computer containing the APR was not locked.

Pour ce fabricant chinois d'API, des nombreux écarts ont été notés :

1.    Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.

During the inspection, FDA investigators discovered a lack of basic laboratory controls to prevent changes to your electronically-stored data and paper records. When you encountered suspect and out-of-specification (OOS) results, you retested samples until you obtained desirable results. You did not investigate, review, or report original results. You relied on incomplete records to evaluate the quality of your drugs and to determine whether your drugs conformed to established specifications and standards...
2.    Failure to prevent unauthorized access or changes to data, and to provide adequate controls to prevent manipulation and omission of data.

During the inspection, we observed that your laboratory systems lacked access controls to prevent deletions or alterations to raw data. For example, our investigator reviewed the electronic folder containing data files generated when your firm tested (b)(4) batches of (b)(4) API for residual solvents by gas chromatography (GC). The investigator compared the file names in the folder with the metadata generated by the Chemstation software you used to operate your GC system, and found that two chromatograms had been deleted from the system. Because there were no controls restricting operators’ or supervisors’ abilities to alter or manipulate the data, an analyst had completed two runs and deleted the results, and then changed the subsequent file names in the folder where reported data was stored to make it appear that the deleted runs never occurred...
3.    Failure to record activities at the time they are performed.

During the inspection, we observed that you did not have worksheets for recording microbial test results and that you failed to contemporaneously document microbial limits test results for (b)(4) API batch (b)(4)....

Enfin le délai de production des enregistrements a également fait l'objet d'une observation:

Delay producing records during inspection

Some records that our investigators requested during the inspection were not available for review.

For example, during the inspection of the microbiology laboratory, our investigators requested the completed microbial QC worksheet for (b)(4) API batch (b)(4). Your laboratory staff led our investigators out of the lab to another room where, according to your staff, the completed document was located. After approximately 30 minutes outside of the laboratory without being provided the completed worksheet, our investigators reentered the microbiology lab and observed a microbiologist with a partially-completed QC worksheet for the batch in question.

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